Method of water treatment using 2,6-substituted aminopyridines and polymer derived therefrom

ABSTRACT

The present invention is a compound of the formula ##STR1## wherein R 1  and R 2  are independently C 1-20  alkyl unsubstituted or substituted with a C 1-3  alcohol, or allyl unsubstituted or substituted with a C 1-4  alkyl or phenyl, R 3  and R 4  are independently hydrogen, or C 1-20  alkyl unsubstituted or substituted with a C 1-3  alcohol or together R 3  and R 4  are oxygen, and R 5  and R 6  are independently C 1-20  alkyl unsubstituted or substituted with C 1-3  alcohol or phenyl, hydroxy, --(CH 2 ) 1-3  COOH, --CHR 7  COOH wherein R 7  is C 1-5  alkyl or C 1-5  alkyl substituted with hydroxy, amino, or carboxy, or allyl unsubstituted or substituted with a C 1-4  alkyl or phenyl or together R 5  and R 6  with the two nitrogen atoms form a fused ring having the formula ##STR2## wherein n is 1 or 2, or form a fused ring having the formula ##STR3## wherein p is an integer from 0 to 3.

This application is a divisional of Ser. No. 07/520,450, filed May 8,1990, U.S. Pat. No. 5,026,802 which is a divisional of Ser. No.07/324,817, filed Mar. 17, 1989, U.S. Pat. No. 4,940,796.

The present invention relates to 4-aminopyridines. In particular, itrelates to substituted 4-aminopyridines.

4-Dialkylaminopyridines are known as acylation and alkylation catalysts.N,N-dimethylaminopyridine (DMAP) has known metals-binding activity. DMAPresidues as pendant groups attached to polymeric backbones are known asmore stable metal-binding reagents.

However, more versatile metal-binding aminopyridines had not beendeveloped. In particular, such versatile aminopyridines that can bestabilized by incorporation directly into a polymeric backbone would beadvantageous.

Accordingly ,the present invention discloses a composition comprising acompound of the formula ##STR4## wherein R¹ and R² are independentlyC₁₋₂₀ alkyl unsubstituted or substituted with a C₁₋₃ alcohol, allylunsubstituted or substituted with a C₁₋₄ alkyl or phenyl, R³ and R⁴ areindependently hydrogen, or C₁₋₂₀ alkyl unsubstituted or substituted witha C₁₋₃ alcohol or together R³ and R⁴ are oxygen, and R⁵ and R⁶ areindependently C₁₋₂₀ alkyl unsubstituted or substituted with C₁₋₃ alcoholor phenyl, hydroxy, --(CH₂)₁₋₃ COOH, --CHR⁷ COOH wherein R⁷ is C₁₋₅alkyl or C₁₋₅ alkyl substituted with hydroxy, amino, or carboxy, orallyl unsubstituted or substituted with a C₁₋₄ alkyl or phenyl ortogether R⁵ and with the two nitrogen atoms form a fused ring having theformula ##STR5## wherein n is 1 or 2, or form a fused ring having theformula ##STR6## wherein p is an integer from 0 to 3. The presentinvention is also a polymer made using a compound of the presentinvention that is polymerizable, an intermediate in making the compoundof the present invention, and a method for using the compound andpolymer of the present invention. The present invention is useful as ametal complexing agent, for example, for the removal of undesirablemetals from waste water by precipitation.

Preferably, the groups R¹ and R² are either allyl or methyl, R³ and R⁴are each hydrogen or together form an oxygen atom, and R⁵ and R⁶ areeach methyl. The most preferred compounds are2,6-bis(N,N-dimethylaminoformyl)-4-(diallylamino)pyridine,2,6-bis(N,N-dimethylaminoformyl)-4-(dimethylamino)pyridine and2,6-bis(N,N-dimethylaminomethyl)-4-(dimethylamino)pyridine.

Polymerizable compounds of the present invention can be used to makeuseful polymers as noted above. The polymer of the present invention hasrepeating units of the formula ##STR7## wherein R³, R⁴, R⁵, and R⁶ areas defined hereinabove, and m is an integer from 10-10,000. PreferablyR³ and R⁴ are each hydrogen or together form an oxygen atom, and R⁵ andR⁶ are each methyl. Preferably, the variable m is an integer from10-1,000, more preferably 50-200. Most preferably, the polymer is a2,6-bis(N,N-dimethylaminoformyl)-4-(diallylamino)pyridine homopolymer orcopolymer with diallylamine, diallylamine derivatives such asdimethyldiallylammonium chloride, diallylformamide, anddiallylacetamide, acrylates such as methacrylic acid, acrylic acid, andtheir alkyl esters, and substituted vinyl monomers such as styrene,N-vinylpyrrolidone, vinyl acetate, and vinyl chloride. Polymerization iscarried out using well known methods for diallylamine polymerization,such as disclosed in Mathias, et al., Journal of Applied PolymerScience, Vol. 33, 1157-1171 (1987).

The intermediate compound of the present invention has the generalformula ##STR8## wherein R⁵ and R⁶ are as defined hereinabove. Thepreferred intermediate compound is2,6-bis(N,N-dimethylaminoformyl)-4-chloropyridine.

The compound of the present invention is preferably made using2,6-bis(chloroformyl)-4-chloropyridine as a starting material. Thiscompound is well known, and can be made by reacting 3-6 molarequivalents of PCl₅ or other chlorine source, such as POCl₃ or SOCl₂,for 12-72 hours at 0°-150° C. with 4-hydroxypyridine-2,6-dicarboxylicacid (chelidamic acid). An intermediate compound of the presentinvention is then made by reacting2,6-bis(chloroformyl)-4-chloropyridine with 2-4 molar equivalents of anamine at -10° to 10° C. for 1-24 hours to produce a2,6-bis(aminoformyl)-4-chloropyridine. Useful amines include ammonia,amino acids such as glycine, alanine, and leucine and their methylesters, aminoalcohols such as ethanolamine, 3-aminopropanol, and4-aminobutanol, diamines or polyamines such as ethanediamine,1,3-propanediamine, and diethylene triamine (NH₂ C₂ H₄ NHC₂ H₄ NH₂),polyaminoethers containing ethylene glycol and diethylene glycol,alkylamines such as dimethylamine and diethylamine, and alkenyl aminessuch as diallylamine and allylmethylamine. Due to the inherently lowerreactivity of the hydroxy group with respect to the amino group,reaction with polyols indicates a higher reaction temperature or longerreaction time. When the amine used is a polyamine, both the polyamineand the intermediate compound are added slowly to a large volume ofsolvent to favor cyclization with respect to the intermolecular action.Thereafter, the 2,6-bis(aminoformyl)-4-chloropyridine is reacted with asecondary amine to produce a 2,6-bis(aminoformyl)-4-aminopyridine.Useful secondary amines include alkylamines such as dimethylamine,diethylamine, dibutylamine, octylamine, undecylamine, eicosylamine,ethanolamine, and propanol amine.

Another preferred method of making a compound of the present inventioneliminates the need to make an intermediate compound. In this process2,6-bis(chloroformyl)-4-chloropyridine is reacted with sufficient amine,preferably 3-6 molar equivalents, to replace all of the chlorine atomsin the starting compound and produce directly a2,6-bis(aminoformyl)-4-aminopyridine.

A further compound of the present invention is made by reacting the2,6-bis(aminoformyl)-4-aminopyridine with 2-4 molar equivalents ofborohydride (BH₃) or other suitable reducing agent, such as lithiumaluminum hydride (LiAlH₄) or borohydride complexed with compounds suchas triethylamine, for 4-28 hours at 20°-50° C. to produce a2,6-bis(aminomethyl)-4-aminopyridine. Exemplary variations of thispreferred compound are made by its reaction with organometalliccompounds, such as alkylmagnesium bromide or alkyl lithium, which yieldsan alkyl group and a hydroxy group at the R³ and R⁴ positions. Furthermodification can then be effected by elimination of the hydroxy groupunder strong acidic conditions and hydrogenation with H₂, which yields ahydrogen atom and the alkyl group at the R³ and R⁴ positions (providedthe alkyl group has at least one hydrogen atom at position 2).Alternative modification is effected when the hydroxy group is replacedby a bromine atom by reacting the hydroxy derivative with PBr₃, formingan organometallic adduct by reacting the bromine derivative with ethercontaining magnesium shavings (effecting a Grignard reagent), and thenreacting the magnesium adduct with an aldehyde to yield a compoundhaving a 2-hydroxy substituted alkyl group and an alkyl group at the R³and ⁴ positions.

The polymer of the present invention is made by polymerizing a freeradical polymerizable compound of the present invention using well knownfree radical polymerization techniques in aqueous media. Suitable freeradical initiators useful in these known techniques include azocompounds, peroxides, and redox initiators. Preferably, azo initiatorsare used. Preferably, the amount of initiator used varies between about0.1 and 10 mole % of tho free radical polymerizable compound used, andthe reaction proceeds until a .polymer having a molecular weight between3,000 and 60,000 (weight average) is obtained.

The compounds and polymers of the present invention are useful as watertreatment chemicals for the removal of metals from water byprecipitation. Examples of metals that can be precipitated from aqueoussolutions, according to the present invention are metals from groups IB,IIB, IIIA and B, IVA and B, VA and B, VIA and B, and VIIB and VIIIB ofthe Mendeleev periodic table, especially copper (Cu), silver (Ag), zinc(Zn), uranium (U), platinum (Pt), or palladium (Pd). Precipitation iseffected by mixing a sufficient amount of the compound or polymer of thepresent invention with water that contains a salt of the metal ofinterest.

In order to more clearly describe the present invention, the followingnon-limiting examples are provided. In the examples, all parts andpercentages are by weight unless indicated otherwise.

EXAMPLE 1 Synthesis of 2,6-bis(chloroformyl)-4-chloropyridine (2)

Chelidamic acid (4-hydroxypyridine-2,6-dicarboxylic acid), (35.15 g,0.192 mol) was suspended in 300 ml dry chloroform (CHCl₃) in a 1 literthree-neck flask provided with Graham condenser, CaCl₂ -moisture trapand magnetic stirrer. The mixture was cooled to 0° C. in an ice bath andPCl₅ (140g, 0.67 mol) was added in a 10 min. period. Gentle bubbling andHCl evolution through the moisture trap was observed after addition ofall PCl₅. The light brown suspension was left overnight at 0° C. It wasthen heated to reflux during 72 hrs and a dark brown solution wasobtained. The reaction flask was cooled to 0° C. and the contents slowlypoured into one liter of an ice-water mixture. Care was taken to avoid atoo-fast addition leading to local temperature increases, which wouldhave caused some hydrolysis of the product along with that of PCl₅.Therefore the temperature was maintained below 10° C. The two-phasemixture was poured into a separation funnel. Some formation of thepartially hydrolyzed diacid 1 was observed as a brown precipitate, whichsettled between the two phases in the separation funnel. The chloroformphase containing 2 was separated and filtered through phase separationfilter paper to remove most of the water. More chloroform was added tospeed up the separation of both phases, which sometimes tended to formemulsions. While maintaining a temperature below 10° C., both phaseswere separated and the organic phase filtered again, this time withphase separation paper. The organic solution was then treated withanhydrous CaCl₂. After filtration, this was rotary evaporated and thedark brown product obtained sublimed in an oil bath at 120° C. under avacuum of 5 mm Hg. The sublimation was repeated and yielded 2 as longwhite needles of melting point 98°-100° C. The product was then storedunder anhydrous conditions. The reaction is represented schematicallybelow. ##STR9##

ALTERNATIVE SYNTHESIS OF 2

Chelidamic acid was reacted with PCl₅ as described above. After pouringinto ice water mixture, hydrolysis to 4-chloro-2,6-pyridine dicarboxylicacid 1 occurred after the mixture was permitted to reach roomtemperature. The brown precipitate formed was filtered and dried undervacuum. It was then refluxed in excess SOCl₂ overnight. Thionyl chloridewas removed by vacuum distillation. The crude acyl chloride 2 wasrecrystallized in CHCl₃ -petroleum ether and purified by sublimation asdescribed above. The reaction is represented schematically below.##STR10##

Synthesis of 2,6-bis(dimethylformamino)-4-chloropyridine (3)

2,6-Bis(chloroformyl)-4-chloropyridine (2) (23.5 g, 0.1 mol) wasdissolved in dry dimethylformamide (72 g) in a three-neck flask (500 ml)provided with thermometer, magnetic stirrer and addition funnel withpressure compensation. The mixture was cooled to 0° C. and a solution ofdimethylamine (27 g) in dry dimethylformamide (75 g) was added throughthe addition funnel. After complete addition, the funnel was replaced bya Liebig condenser and the mixture heated 2 hrs at 80° C. A vacuumdistillation head was attached and most of the dimethylformamidedistilled. Aqueous KOH was added to the remaining product to raise thepH to 11. This was then extracted with CHCl₃, filtered with phaseseparation paper, and rotary evaporated. The resulting white crystalswere 99% pure (as determined by comparing peak areas of a gaschromatograph of a chloroform solution using a fused silica megaborecolumn with 5% phenyl-methyl polysiloxane and flame ionization detector)with a melting point of 138°-140° C.

The yield was approximately 40%. The reaction is representedschematically below. ##STR11##

EXAMPLE 2 Synthesis of the monomer2,6-Bis(N,N-dimethylaminoformyl)-4-(diallylamino)pyridine (4)

2,6-Bis(dimethylformamino)-4-chloropyridine (3) (8.7 g, 0.039 mol) wasrefluxed with freshly distilled diallylamine (30 ml) in a three-neckflask (100 ml) provided with Liebig condenser with N₂ inlet, thermometerand magnetic stir bar. After 72 hrs, 98% conversion was achieved(followed by GC) and the reflux (110° C.) was stopped. The reactionmixture was shaken with excess 10% NaOH and extracted with CHCl₃. Theorganic phase was then filtered with phase separation filter paper androtary evaporated. Distillation under vacuum yielded a product stillcontaminated with diallylamine. A 95% pure product was obtained byrecrystalization from ethyl acetate - cyclohexane (50/50). Higher puritywas obtained using column chromatography on silica gel. First, unreacted3 was eluted with ethyl acetate. The compound 4 was eluted with methanoland, after concentration, was 99% pure by gas chromatography (GC),determined as in EXAMPLE 1. The reaction is represented schematicallybelow. ##STR12##

EXAMPLE 3 Polymerization of the monomer2,6-Bis(N,N-dimethylaminoformyl)-4-(diallylamino)pyridine (4)

2,6-Bis(N,N-dimethylaminoformyl)-4-(diallylamino)pyridine (4) (1.72 g,5.5×10⁻³ mol), 5 ml H₂ O, 0.7 ml conc. HCl and2,2'-azobis(2-amidinopropane) hydrochloride catalyst (V50, WakoChemicals USA) (0.015 g, 5.5×10⁻⁵ mol) were charged into a 50 ml Schlenkflask. The solution was submitted to three freeze-thaw cycles andimmersed in a water bath at 60° C. Additional catalyst (0.24 g) wasadded after 30 hours. Precipitation of a pale yellow solid was observedafter two days. Polymerization was stopped after five days. Theprecipitate was filtered, washed with water, and the wash water wascombined with the yellow supernatant liquid, which was enclosed incellulose dialysis membranes having a pore size sufficient to filterpolymers having a molecular weight greater than 3,000-6,000 weightaverage molecular weight, i.e., they have a molecular weigh cut-off of3,000-6,000. The bags were then immersed in fresh water for three days,after which the bag contents were freeze dried. The freeze-died polymerwas a Yellow-orange powder, very soluble in water and methanol, butinsoluble in THF(tetrahydrofurane) or CHCl₃. The reaction is representedschematically below. ##STR13##

Chelating activity of the homopolymer of 4

Chelating activity of the homopolymer of2,6-bis(dimethylformamido)-4-diallylamino-pyridine (4) with cupric saltswas demonstrated to show that the homopolymer is useful in removingmetals from water by precipitation. A ¹³ C NMR spectrum (number ofscans: 2254) of the polymer was taken. A concentrated Cu(NO₃)₂ solutionwas added to the polymer at a 0.2 metal/polymer ratio, which led toinstantaneous precipitation of a green product, which was redissolved inexcess polymer. Comparison of a ¹³ C NMR spectrum (number of scans:1217) taken after addition of the metal salt with the spectrum of thepolymer before addition of the metal salt showed decrease of intensityof the absorption peaks of the 3-pyridine carbons at 105 ppm and thecarbonyl carbons at 177 ppm which indicated complexing with the metal.All spectra were recorded on a Bruker MSL-200 instrument at .roomtemperature with TMS (tetramethylsilane) as chemical shift standard.

EXAMPLE 4

Copolymerization of the monomer 4 (1.00 g, 3.20×10⁻³ mol) withdiallylamine (1.00 g, 1.03×10⁻² mol) was carried out under the sameconditions as in EXAMPLE 3, except that no additional catalyst was addedafter 30 hours and polymerization was stopped after 72 hours. Filteringand dialysis was carried out as in EXAMPLE 3. The freeze dried productwas a white-yellow glassy material, which was soluble in water andmethanol, but insoluble in THF an chloroform. The presence of pyridinerings in the final product was determined by ¹³ C-NMR spectroscopy.

EXAMPLE 5 Synthesis cf2,6-bis(N,N-dimethylaminoformyl)-4-(dimethylamino)pyridine (5)

2,6-Bis(chloroformyl)-4-chloropyridine (2) (5 g, 0.06 mol) was dissolvedin dry dimethylformamide (60 ml) in a three-neck flask (500 ml) providedwith thermometer, magnetic stirrer and addition funnel. A solution ofdimethylamine (29 g) in dry dimethylformamide (72 g) was added slowlyunder stirring through the addition funnel. The flask was kept at roomtemperature for 6 hours and then heated 6 hours at 80° C. Stirring atroom temperature was continued overnight. Dimethylformamide was thendistilled off under vacuum. The yellow product remaining in the flaskwas dissolved in 200 ml NaOH 10% and extracted with four portions ofCHCl₃ (50 ml each). After filtration with phase separation filter paperthe solvent was rotary evaporated. Recrystalization in CHCl₃-cyclohexane yields white crystals of melting point 175°-178° C. Thereaction is represented schematically below. ##STR14##

Chelating activity of the compound 5

All spectra here recorded on a Bruker MSL-200 instrument at roomtemperature with TMS (tetramethylsilane) as chemical shift standard. A¹³ C-NMR spectrum (number of scans: 2034) of compound 5 in water wastaken. After addition to the compound of a manganese salt (MnCl₂.4H₂ O)at a metal/ligand ratio of 0.0032 a second ¹³ C-NMR spectrum (number ofscans: 1536) was made. The peak corresponding to the carbonyl carbon inthe first spectrum disappears in the second, while the other peaksexperience only slight broadening. The largest distortion of thespectrum was expected in the absorption of those nuclei closest to thecomplexed metal ion. The vanishing of the carbonyl carbon signalindicated that complexation had taken place in that proximity. Thisdemonstrated that the compound is useful in removing metals from waterby precipitation.

EXAMPLE 6 Synthesis of2,6-Bis(N,N-dimethylaminomethyl)-4-(dimethylamino)pyridine (6)

A three-neck flask (500 ml) provided with dropping funnel, refluxcondenser and magnetic stir bar was dried at 100° C. and allowed to coolto room temperature in a dry N₂ atmosphere.2,6-bis(N,N-dimethlaminoformyl )-4-(dimethylamino)pyridine (5) (5 g,0.019 mol) was suspended in dry THF (20 ml) and cooled to 0° C. BH₃ -THFsolution (120 g, 0.08 mol BH₃) was transferred by means of a hypodermicsyringe into the dropping funnel. The solution was then added in a 20min. period under stirring and cooling. After 2 hours the whitesuspension was refluxed for 48 hours during which it turned into a palegreen solution. 6M HCl (200 ml) was then added at 0° C. under stirringwhereby H₂ gas evolves. THF was distilled at atmospheric pressure; theamine-borane complex was then destroyed (further H₂ evolution). Afterleaving overnight at room temperature, NaOH pellets were slowly addedunder cooling and stirring until pH 11 was reached. The solution wastransferred to a separation funnel (some H₂ O had to be added toredissolve NaCl) and extracted with CH₂ Cl₂. The organic phase wasfiltered through phase separation filter paper and rotary evaporated.The final solvent removal in high vacuum yielded 2.2 g of a greenishwhite, slightly fishy smelling syrup that solidified in therefrigerator. The product was 99% pure by GC and its structure wasconfirmed by ¹ H and ¹³ C-NMR spectroscopy and elementary analysis.##STR15##

What is claimed is:
 1. A method of water treatment comprising mixing a polymer having repeating units of the formulawherein R¹ and R² are independently C₁₋₂₀ alkyl unsubstituted or substituted with a C₁₋₃ alcohol, or allyl unsubstituted or substituted with a C₁₋₄ alkyl or phenyl, R³ and R⁴ are independently hydrogen, or C₁₋₂₀ alkyl unsubstituted or substituted with a C₁₋₃ alcohol or together R³ and R⁴ are oxygen, and R⁵ and R⁶ are independently C₁₋₂₀ alkyl unsubstituted or substituted with C₁₋₃ alcohol or phenyl, hydroxy, --(CH₂)₁₋₃ COOH, --CHR⁷ COOH wherein R⁷ is C₁₋₅ alkyl or C₁₋₅ alkyl substituted with hydroxy, amino, or carboxy, or allyl unsubstituted or substituted with a C₁₋₄ alkyl or phenyl or together R⁵ and R⁶ with the two nitrogen atoms form a fused ring having the formula ##STR16## wherein n is 1 or 2, or form a fused ring having the formula ##STR17## wherein p is an integer from 0 to 3, and m is an integer from 10-10,000 with water containing a metal salt to form a precipitate of the metal complexed with the polymer.
 2. The method of claim 1 wherein R¹ and R² are each allyl or methyl.
 3. The method of claim 1 wherein R³ and R⁴ are each hydrogen or together oxygen.
 4. The method of claim 1 wherein R⁵ and R⁶ are independently C₁ -C₄ alkyl. 